{"gene":"TG_206590","gene_symbol":"CDPK2A","run_date":"2026-09-08T11:06:17","timeline":{"discoveries":[{"year":2023,"finding":"CDPK2A is a calcium-dependent protein kinase that contributes to Toxoplasma lytic cycle fitness by regulating microneme discharge, gliding motility, and egress from infected host cells, as demonstrated by chemical-genetic (analog-sensitive kinase allele) and conditional-depletion approaches.","method":"Chemical-genetic (analog-sensitive kinase alleles) and conditional protein depletion with phenotypic readouts (microneme discharge, gliding motility, egress assays)","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional depletion and chemical-genetic approaches with multiple orthogonal phenotypic readouts in a single lab study","pmids":["37610220"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"Genetic epistasis analysis revealed that CDPK2A acts upstream of CDPK1 in a signaling module governing motility and egress, with partial functional redundancy between the two kinases.","method":"Genetic epistasis using analog-sensitive kinase alleles combined with conditional depletion of CDPK2A and CDPK1","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis established via two complementary chemical-genetic approaches (analog-sensitive alleles and conditional depletion), single lab","pmids":["37610220"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"CDPK2A is a calcium-dependent protein kinase that functions upstream of CDPK1 in a signaling module to regulate microneme discharge, gliding motility, and host-cell egress in Toxoplasma gondii, with partial functional redundancy with CDPK1."},"narrative":{"mechanistic_narrative":"CDPK2A is a calcium-dependent protein kinase that contributes to the Toxoplasma gondii lytic cycle by regulating microneme discharge, gliding motility, and egress from infected host cells [PMID:37610220]. Chemical-genetic and conditional-depletion analyses place CDPK2A upstream of CDPK1 within a signaling module governing motility and egress, and the two kinases are partially functionally redundant [PMID:37610220]. Beyond this signaling relationship and the associated lytic-cycle phenotypes, no direct substrates, structural determinants, or activation mechanism of CDPK2A have been characterized in the available corpus.","teleology":[{"year":2023,"claim":"Establishing whether CDPK2A has a functional role in the parasite lytic cycle, this work showed it is a calcium-dependent kinase required for efficient microneme discharge, gliding motility, and host-cell egress.","evidence":"Analog-sensitive kinase alleles and conditional protein depletion with microneme discharge, gliding, and egress readouts in Toxoplasma gondii","pmids":["37610220"],"confidence":"Medium","gaps":["No direct phosphorylation substrates of CDPK2A identified","No structural or biochemical characterization of the kinase's calcium-dependent activation","Single-lab study"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"To resolve how CDPK2A relates to the known egress kinase CDPK1, epistasis analysis positioned CDPK2A upstream of CDPK1 in a shared signaling module with partial redundancy between the two.","evidence":"Genetic epistasis using analog-sensitive kinase alleles combined with conditional depletion of CDPK2A and CDPK1 in Toxoplasma gondii","pmids":["37610220"],"confidence":"Medium","gaps":["Molecular basis of CDPK2A-to-CDPK1 signaling not defined","Extent and mechanism of functional redundancy unquantified","Whether CDPK2A directly regulates CDPK1 or acts through intermediates is unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The direct substrates, activation mechanism, and molecular link between CDPK2A and CDPK1 remain undefined.","evidence":"No discovery in the timeline addresses substrate identification or the biochemical basis of the CDPK2A-CDPK1 relationship","pmids":[],"confidence":"Medium","gaps":["No phosphoproteomic substrate mapping","No structural model of CDPK2A","Mechanism of upstream regulation of CDPK1 unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["CDPK1 (ACTS DOWNSTREAM OF CDPK2A IN A SHARED SIGNALING MODULE, PARTIALLY REDUNDANT)"],"other_free_text":["Regulates microneme discharge, gliding motility, and host-cell egress in the Toxoplasma gondii lytic cycle [#0]","Functions upstream of CDPK1 with partial functional redundancy [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"37610220","id":"PMC_37610220","title":"CDPK2A and CDPK1 form a signaling module upstream of Toxoplasma motility.","date":"2023","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/37610220","citation_count":12,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2763,"output_tokens":551,"usd":0.008277,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5253,"output_tokens":1428,"usd":0.030982,"stage2_stop_reason":"end_turn"},"total_usd":0.039259,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"CDPK2A is a calcium-dependent protein kinase that contributes to Toxoplasma lytic cycle fitness by regulating microneme discharge, gliding motility, and egress from infected host cells, as demonstrated by chemical-genetic (analog-sensitive kinase allele) and conditional-depletion approaches.\",\n      \"method\": \"Chemical-genetic (analog-sensitive kinase alleles) and conditional protein depletion with phenotypic readouts (microneme discharge, gliding motility, egress assays)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional depletion and chemical-genetic approaches with multiple orthogonal phenotypic readouts in a single lab study\",\n      \"pmids\": [\"37610220\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Genetic epistasis analysis revealed that CDPK2A acts upstream of CDPK1 in a signaling module governing motility and egress, with partial functional redundancy between the two kinases.\",\n      \"method\": \"Genetic epistasis using analog-sensitive kinase alleles combined with conditional depletion of CDPK2A and CDPK1\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis established via two complementary chemical-genetic approaches (analog-sensitive alleles and conditional depletion), single lab\",\n      \"pmids\": [\"37610220\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CDPK2A is a calcium-dependent protein kinase that functions upstream of CDPK1 in a signaling module to regulate microneme discharge, gliding motility, and host-cell egress in Toxoplasma gondii, with partial functional redundancy with CDPK1.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CDPK2A is a calcium-dependent protein kinase that contributes to the Toxoplasma gondii lytic cycle by regulating microneme discharge, gliding motility, and egress from infected host cells [#0]. Chemical-genetic and conditional-depletion analyses place CDPK2A upstream of CDPK1 within a signaling module governing motility and egress, and the two kinases are partially functionally redundant [#1]. Beyond this signaling relationship and the associated lytic-cycle phenotypes, no direct substrates, structural determinants, or activation mechanism of CDPK2A have been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Establishing whether CDPK2A has a functional role in the parasite lytic cycle, this work showed it is a calcium-dependent kinase required for efficient microneme discharge, gliding motility, and host-cell egress.\",\n      \"evidence\": \"Analog-sensitive kinase alleles and conditional protein depletion with microneme discharge, gliding, and egress readouts in Toxoplasma gondii\",\n      \"pmids\": [\"37610220\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct phosphorylation substrates of CDPK2A identified\",\n        \"No structural or biochemical characterization of the kinase's calcium-dependent activation\",\n        \"Single-lab study\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"To resolve how CDPK2A relates to the known egress kinase CDPK1, epistasis analysis positioned CDPK2A upstream of CDPK1 in a shared signaling module with partial redundancy between the two.\",\n      \"evidence\": \"Genetic epistasis using analog-sensitive kinase alleles combined with conditional depletion of CDPK2A and CDPK1 in Toxoplasma gondii\",\n      \"pmids\": [\"37610220\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular basis of CDPK2A-to-CDPK1 signaling not defined\",\n        \"Extent and mechanism of functional redundancy unquantified\",\n        \"Whether CDPK2A directly regulates CDPK1 or acts through intermediates is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct substrates, activation mechanism, and molecular link between CDPK2A and CDPK1 remain undefined.\",\n      \"evidence\": \"No discovery in the timeline addresses substrate identification or the biochemical basis of the CDPK2A-CDPK1 relationship\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No phosphoproteomic substrate mapping\",\n        \"No structural model of CDPK2A\",\n        \"Mechanism of upstream regulation of CDPK1 unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004683\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006935\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CDPK1 (acts downstream of CDPK2A in a shared signaling module, partially redundant)\"],\n    \"other_free_text\": [\n      \"Regulates microneme discharge, gliding motility, and host-cell egress in the Toxoplasma gondii lytic cycle [#0]\",\n      \"Functions upstream of CDPK1 with partial functional redundancy [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_206590","name":"CDPK2A","product":"calcium-dependent protein kinase CDPK2A","uniprot_acc":"S8F5F3","chromosome":"TGME49_chrVIIa","start_pos":798833},{"strain":"GT1","gene_id":"TGGT1_206590","name":null,"product":"calcium-dependent protein kinase CDPK2A","uniprot_acc":null,"chromosome":"TGGT1_chrVIIa","start_pos":775466},{"strain":"RH88","gene_id":"TGRH88_033430","name":null,"product":"calcium-dependent protein kinase CDPK2A","uniprot_acc":null,"chromosome":"CM023088","start_pos":879827},{"strain":"VEG","gene_id":"TGVEG_206590","name":null,"product":"calcium-dependent protein kinase CDPK2A","uniprot_acc":"A0A125YR92","chromosome":"TGVEG_chrVIIa","start_pos":856895}]}